Devices and Methods For Controlling Patient Temperature

ABSTRACT

Relatively non-invasive devices and methods for heating or cooling a patient&#39;s body are disclosed. Devices and methods for treating ischemic conditions by inducing therapeutic hypothermia are disclosed. Devices and methods for inducing therapeutic hypothermia through esophageal cooling are disclosed. Devices and methods for operative temperature management are disclosed.

RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.12/713,644, which was filed on Feb. 26, 2010 and claimed the priority ofU.S. provisional application Ser. No. 61/155,876, which was filed onFeb. 26, 2009, the disclosures of which are hereby incorporated byreference in their entireties.

FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

[Not Applicable]

MICROFICHE/COPYRIGHT REFERENCE

[Not Applicable]

BACKGROUND OF THE INVENTION

In industrial countries, 36 to 128 per 100,000 inhabitants per yearexperience a sudden out-of-hospital cardiac arrest (“OHCA”) withsurvival remaining a rare event. Cardiovascular disease affects anestimated 80,700,000 North American adults, with approximately 2400individuals dying from cardiovascular disease daily (an average of onedeath every 37 seconds). Approximately 310,000 coronary heart diseasedeaths due to OHCA occur annually.

According to data reported by the National Registry of CardiopulmonaryResuscitation in 2007, over 75% of patients having cardiopulmonaryarrest events did not survive the event. For those who did survive theevent, an additional 35.2% died afterward.

In the 1950s, moderate hypothermia (body temperature of approximately28° C. to approximately 32° C.) and deep hypothermia (body temperatureof approximately <28° C.) were utilized for various surgical proceduresas well as experimentally to reverse neurological insults associatedwith cardiac arrest. However, because of the numerous complications ofmoderate-to-deep hypothermia and the difficulty in inducing thesetemperature reductions, enthusiasm for the use of therapeutichypothermia waned. Consequently, the use of hypothermia to help reversethe neurologic insult after normothermic cardiac arrest lay dormant forseveral decades. However, beginning in the late 1980s, positive outcomesfollowing cardiac arrest were reported in dogs with mild hypothermia.

Contemporary use of mild therapeutic hypothermia following cardiacarrest in human patients is supported by recent randomized controltrials and a meta-analysis of individual patient data. Majororganizations, including the International Liaison Committee onResuscitation (“ILCOR”) and the American Heart Association (“AHA”),recommend the induction of mild therapeutic hypothermia for comatosecardiac arrest survivors. However, the AHA therapeutic hypothermiaguidelines lack a concrete description of exactly how to cool patients.

Despite widespread support for mild therapeutic hypothermia in thecontext of cardiac arrest, including consensus recommendations frommajor resuscitative organizations, the use of mild therapeutichypothermia in clinical practice remains low. Many clinicians reportthat therapeutic hypothermia is too technically difficult to achieve inpractice.

In addition, health care professionals occasionally need to inducehypothermia during certain surgical procedures or prevent inadvertenthypothermia and the multiple adverse effects that result fromuncontrolled and unintended deviations from normal body temperature.

Control of a patient's body temperature while undergoing surgicalprocedures in the operating room is beneficial because, for instance,even mild inadvertent hypothermia during operative procedures increasesthe incidence of wound infection, prolongs hospitalization, increasesthe incidence of morbid cardiac events and ventricular tachycardia, andimpairs coagulation.

Even mild hypothermia (<1° C.) significantly increases blood loss byapproximately 16% and increases the relative risk for transfusion byapproximately 22%, while maintaining perioperative normothermia reducesblood loss and transfusion requirement by clinically important amounts.

Because considerable strong evidence shows that thermal managementimproves outcomes in a variety of surgical patients, the currentAmerican Heart Association-American College of Cardiology 2007Guidelines on Perioperative Cardiovascular Evaluation and Care forNoncardiac Surgery include a Level 1 recommendation for maintenance ofperioperative normothermia.

Moreover, recognizing the numerous complications of perioperativehypothermia, the American Society of Anesthesiologists (ASA) hasrecently recommended that postoperative temperature become a basis forassessing physician compliance with current guidelines on the preventionof hypothermia.

Although inadvertent operative hypothermia is considered one of the mostpreventable surgical complications, existing methods to control bodytemperature are limited in efficacy, such that the incidence ofinadvertent operative hypothermia for surgical patients can exceed 50%.

Currently available methods to control body temperature include bothnon-invasive and invasive techniques. For example, the most commonlyused techniques developed to induce therapeutic hypothermia includesurface cooling and invasive cooling.

Surface cooling is relatively simple to use, and can be accomplished bythe use of external vests, cooling helmets, circulating cold-waterblankets, cold forced-air blankets, or with less sophisticated methods,such as ice packs and cold-water immersion, but takes between 2 and 8hours to reduce core body temperature. Surface cooling is limited by therate at which cooling can occur, due to the tendency of blood flow to beshunted away from skin and towards the core. External devices, such asvests or blankets, significantly limit access to important patient areasthat are often needed in critical care, such as for catheter placement,and require removal or modification to perform CPR. Surface coolingtechniques such as ice packs limit the precision with which a patient'stemperature can be controlled. Cooling with ice packs and conventionalcooling blankets often results in unintentional overcooling.

As another example, several methods are utilized to warm a patient, andinclude raising the operating room temperature and using externalwarming devices, such as forced-air warming blankets.

Several issues exist with these current methods: (1) excessively warmroom temperature creates an uncomfortable environment for the surgicalteam, (2) forced-air warmers are bulky and may impact the surgicalfield; they tend to be inefficient and must be used for extended periodsof time in the operating room, and (3) none of these systems adequatelycontrol or manage temperature, leading to both overheating or, moreoften, inadequate warming.

Rasmussen et al. (Forced-air surface warming versus oesophageal heatexchanger in the prevention of perioperative hypothermia. ActaAnaesthesiol Scand. March 1998; 42(3):348-52) mention that forced-airwarming of the upper part of the body is effective in maintainingnormothermia in patients undergoing abdominal surgery of at least 2 hexpected duration, while central heating with an esophageal heatexchanger does not suffice to prevent hypothermia. Brauer et al.(Oesophageal heat exchanger in the prevention of perioperativehypothermia. Acta Anaesthesiol Scand. March 1998; 42(10):1232-33) statesthat an esophageal heat exchanger can only add a small amount of heat tothe overall heat balance of the body.

Invasive temperature management treatments include: the infusion of coldintravenous fluids; the infusion of warmed intravenous fluids; coldcarotid infusions; single carotid artery perfusion with extracorporealcooled blood; cardiopulmonary bypass; ice water nasal lavage; coldperitoneal lavage; nasogastric and rectal lavage; and the placement ofinvasive intravenous catheters connected to refrigerant or heat exchange(warming) devices. Invasive temperature management treatments oftenrequire significant personnel involvement and attention to performsuccessfully. Moreover, certain invasive temperature managementmodalities have been associated with overcooling, overheating, or, moreoften, inadequate warming.

The use of intravenous fluid as a temperature management modality hasthe undesirable effect of contributing to circulating fluid volumeoverload, and has been found to be insufficient for maintaining targettemperature. In addition, large volumes of fluids must be infused toobtain a significant effect.

Other techniques for achieving hypothermia include blood cooling throughinhaled gases and the use of balloon catheters.

However, Andrews et al. (Randomized controlled trial of effects of theairflow through the upper respiratory tract of intubated brain-injuredpatients on brain temperature and selective brain cooling. Br. J.Anaesthesia. 2005; 94(3):330-335) mention that a flow of humidified airat room temperature through the upper respiratory tracts of intubatedbrain-injured patients did not produce clinically relevant orstatistically significant reductions in brain temperature.

Dohi et al. (Positive selective brain cooling method: a novel, simple,and selective nasopharyngeal brain cooling method. ActaNeurochirgurgica. 2006; 96:409-412) mention that a Foley ballooncatheter inserted to direct chilled air into the nasal cavity, when usedin combination with head cooling by electric fans, was found toselectively reduce brain temperature.

Holt et al. (General hypothermia with intragastric cooling. Surg.Gynecol Obstet. 1958; 107(2):251-54; General hypothermia withintragastric cooling: a further study. Surg Forum. 1958; 9:287-91)mention using an intragastric balloon in combination with thermicblankets to produce hypothermia in patients undergoing surgicalprocedures.

Likewise, Barnard (Hypothermia: a method of intragastric cooling. Br. J.Surg. 1956; 44(185):296-98) mentions using an intragastric balloon forinducing hypothermia by intragastric cooling.

US Patent Application Publication 2004/0199229 to Lasheras mentionsheating or cooling via a balloon inserted into a patient's colon.

US Patent Application Publication 2004/0210281 to Dzeng et al. mentionsa transesophageal balloon catheter for specifically cooling the heartand disparages technologies that cool the entire body.

US Patent Application Publication 2007/0055328 to Mayse et al. mentionsa balloon catheter for protecting the digestive tract of a personundergoing cardiac ablation to correct cardiac arrhythmia.

U.S. Pat. No. 6,607,517 to Dae et al. is generally directed to usingendovascular cooling to treat congestive heart failure.

Several complications are known to result from increasing pressurewithin the gastrointestinal tract, as may occur with a balloon inflatedwithin the stomach, colon, or other gastrointestinal organ. For example,stomach inflation may trigger intestinal rupture, regurgitation andaspiration that may result in pneumonia, esophageal tears, colonnecrosis, and gut ischemia.

In addition, several temperature-controlling modalities, particularlythose that employ inflatable balloons, limit access of the health careprovider to particular anatomical structures that may be crucial forpatient care, such as the stomach. These modalities may require removalor modification to achieve proper treatment.

To date, no available modality for controlling patient temperature hasbeen found that sufficiently overcomes the technical, logistical, andfinancial barriers that exist. The ideal patient temperature controldevice has yet to be developed.

In summary, the state of the art related to the control of patienttemperature comprises at least one significant long felt need: methodsand devices for efficient, safe, and rapid control of patienttemperature while maintaining access to anatomical areas necessary foradditional treatment. The present technology identifies severalindications, diseases, disorders, and conditions that can be treated orprevented by controlling patient temperature and, further, providesrelatively non-invasive methods and devices for rapidly and efficientlycontrolling patient temperature while reducing the risks posed by priordevices and methods. Moreover, certain embodiments of the presenttechnology provide relatively non-invasive methods and devices forrapidly and efficiently controlling patient temperature, while at thesame time maintaining access to important anatomical structures.

BRIEF SUMMARY OF THE INVENTION

At least one aspect of the present technology provides one or moremethods for inducing systemic hypothermia. The methods compriseinserting a heat transfer device, including a fluid path defined by aninflow lumen and an outflow lumen, into a patient's esophagus;initiating flow of a cooling medium along the fluid path; andcirculating the medium along the fluid path for a time sufficient toinduce systemic hypothermia in the patient. The heat transfer device mayinclude a discrete heat transfer region that is confined to thepatient's esophagus. The patient may be maintained in a state ofhypothermia for at least about two hours, for example. The methods mayfurther comprise monitoring at least one physiological parameter of thepatient, such as body temperature. The methods may further comprisemaintaining the patient's body temperature below about 34° C.

At least one aspect of the present technology provides one or moremethods for controlling core body temperature in a subject. The methodscomprise inserting a heat transfer device, including a fluid pathdefined by an inflow lumen and an outflow lumen, into a subject'sesophagus; initiating flow of a heat transfer medium along the fluidpath; and circulating the medium along the fluid path for a timesufficient to control core body temperature in a subject. The heattransfer device may include a discrete heat transfer region that isconfined to the patient's esophagus. The core body temperature of thesubject may be controlled for at least about two hours, for example. Themethods may further comprise monitoring at least one physiologicalparameter of the subject, such as body temperature. The methods mayfurther comprise maintaining the patient's body temperature, forexample, below about 34° C., between about 34° C. and about 37° C., orat about 37° C.

At least one aspect of the present technology provides one or moreesophageal heat transfer devices. The devices comprise: a plurality oflumens configured to provide a fluid path for flow of a heat transfermedium; a proximal end including an input port and an output port; adistal end configured for insertion into a patient's esophagus. Thedevices may further comprise a hollow tube having a distal endconfigured to extend into the patient's stomach. The devices may furthercomprise an anti-bacterial coating.

At least one aspect of the present technology provides one or moremethods for treating or preventing ischemia-reperfusion injury or injurycaused by an ischemic condition. The methods comprise inserting a heattransfer device, including a fluid path defined by an inflow lumen andan outflow lumen, into a patient's esophagus; initiating flow of acooling medium along the fluid path; and circulating the cooling mediumalong the fluid path for a time sufficient to induce systemichypothermia in the patient.

At least one aspect of the present technology provides one or moremethods for treating or preventing neurological or cardiac injury. Themethods comprise inserting a heat transfer device, including a fluidpath defined by an inflow lumen and an outflow lumen, into a patient'sesophagus; initiating flow of a cooling medium along the fluid path; andcirculating the cooling medium along the fluid path for a timesufficient to induce systemic hypothermia in the patient. Theneurological injury may be associated with, for example, stroke(including ischemic stroke), traumatic brain injury, spinal cord injury,subarachnoid hemorrhage, out-of-hospital cardiopulmonary arrest, hepaticencephalopathy, perinatal asphyxia, hypoxic-anoxic encephalopathy,infantile viral encephalopathy, near-drowning, anoxic brain injury,traumatic head injury, traumatic cardiac arrest, newbornhypoxic-ischemic encephalopathy, hepatic encephalopathy, bacterialmeningitis, cardiac failure, post-operative tachycardia, or acuterespiratory distress syndrome (“ARDS”).

At least one aspect of the present technology provides one or moremethods for treating myocardial infarction, stroke, traumatic braininjury, or ARDS. The methods comprise inducing mild therapeutichypothermia in a patient. Mild therapeutic hypothermia may be inducedvia esophageal cooling. The patient may be maintained in a state ofhypothermia for at least about two hours, for example. The methods mayfurther comprise monitoring at least one physiological parameter of thepatient, such as body temperature. The methods may further comprisemaintaining the patient's body temperature below about 34° C.

At least one aspect of the present technology provides one or moremethods for treating myocardial infarction, stroke, traumatic braininjury, or ARDS. The methods comprise inserting a heat transfer device,including a fluid path defined by an inflow lumen and an outflow lumen,into a patient's esophagus; initiating flow of a cooling medium alongthe fluid path; and circulating the cooling medium along the fluid pathfor a time sufficient to induce systemic hypothermia in the patient.

At least one aspect of the present technology provides one or moremethods for treating cardiac arrest. The methods comprise inducingsystemic hypothermia via esophageal cooling. The methods may furthercomprise inserting a heat transfer device, including a fluid pathdefined by an inflow lumen and an outflow lumen, into a patient'sesophagus; initiating flow of a cooling medium along the fluid path; andcirculating the cooling medium along the fluid path for a timesufficient to induce systemic hypothermia in the patient.

At least one aspect of the present technology provides one or moremethods for operative temperature management. The methods comprisecontrolling a patient's core body temperature via esophageal cooling.The methods may further comprise inserting a heat transfer device,including a fluid path defined by an inflow lumen and an outflow lumen,into a patient's esophagus; initiating flow of a heat transfer mediumalong the fluid path; and circulating the heat transfer medium along thefluid path for a time sufficient to control the patient's core bodytemperature.

At least one aspect of the present technology provides one or moredevices for cooling or warming at least one portion of a patient's body.The devices comprise a heat transfer device including a proximal end, adistal end, and at least one flexible tube extending the proximal anddistal end. The proximal end includes a heat transfer medium input portand a heat transfer medium output port. The distal end is configured forinsertion into an orifice of a patient. The flexible tube defines aninflow lumen and an outflow lumen and the lumens may be configured toprovide a fluid path for flow of a heat transfer medium. The devicesfurther comprise a supply line connected to the input port and a returnline connected to the output port.

The device may be used to treat or prevent, for example, injury causedby an ischemic condition; ischemia-reperfusion injury; neurologicalinjury; cardiac injury. The device may be used to treat patients whohave experienced or are experiencing myocardial infarction; stroke;traumatic brain injury; or ARDS. The methods of treating or preventingsuch conditions or diseases comprise inserting the distal end of theheat transfer device nasally or orally; advancing the distal end intothe patient's esophagus; initiating flow of a cooling medium along thefluid path; and circulating the cooling medium along the fluid path fora time sufficient to induce systemic hypothermia in the patient. Thepatient may be maintained in a state of hypothermia for at least twohours. The methods may further comprise monitoring at least onephysiological parameter of the patient, such as body temperature. Themethods may further comprise maintaining the patient's body temperaturebelow about 34° C.

The device may be used to control a patient's core body temperatureduring, for example, surgical procedures. The methods of controlling thepatient's core body temperature comprise inserting the distal end of theheat transfer device nasally or orally; advancing the distal end intothe patient's esophagus; initiating flow of a heat transfer medium alongthe fluid path; and circulating the heat transfer medium along the fluidpath for a time sufficient to control core body temperature in thepatient. The core body temperature of the subject may be controlled forat least about two hours, for example. The methods may further comprisemonitoring at least one physiological parameter of the subject, such asbody temperature. The methods may further comprise maintaining thepatient's body temperature, for example, below about 34° C., betweenabout 34° C. and about 37° C., or at about 37° C.

At least one aspect of the present technology provides an esophagealheat transfer device comprising (a) a plurality of lumens configured toprovide a fluid path for flow of a heat transfer medium; (b) a heattransfer region configured for contacting esophageal epithelium of apatient; (c) a proximal end including an input port and an output port;and (d) a distal end configured for insertion into an esophagus of apatient. The heat transfer device can also comprise a hollow tube havinga distal end configured to extend into the patient's stomach. The heattransfer device can be capable of contacting substantially all of thepatient's esophageal epithelium. The heat transfer device can comprise asemi-rigid material. The heat transfer device can be capable of coolingat a rate of about 1.2° C./hr to about 1.8° C./hr. The heat transferdevice can be capable of cooling a mass at a rate of about 350 kJ/hr toabout 530 kJ/hr, and, in particular, at a rate of about 430 kJ/hr. Theheat transfer device can include a heat transfer region with a surfacearea of at least about 100 cm² and, in particular, a surface area ofabout 140 cm².

At least one aspect of the present technology provides a system forcooling or warming at least one portion of a patient's body, comprisinga heat transfer device including a proximal end, a distal end, and atleast one semi-rigid tube extending between the proximal and distalends; a supply line; and a return line. The proximal end of the heattransfer device includes a heat transfer medium input port and a heattransfer medium output port. The distal end of the heat transfer deviceis configured for insertion into an orifice of a patient, such as theesophageal lumen. The semi-rigid tube defines an inflow lumen and anoutflow lumen and the lumens are configured to provide a fluid path forflow of a heat transfer medium. The supply line is connected to theinput port and the return line is connected to the output port. The heattransfer device can also comprise a hollow tube having a distal endconfigured to extend into the patient's stomach. The heat transferdevice can be capable of contacting substantially all of the patient'sesophageal epithelium. The heat transfer device can comprise asemi-rigid material. The heat transfer device can be capable of coolingat a rate of about 1.2° C./hr to about 1.8° C./hr. The heat transferdevice can be capable of cooling a mass at a rate of about 350 kJ/hr toabout 530 kJ/hr, and, in particular, at a rate of about 430 kJ/hr. Theheat transfer device can include a heat transfer region with a surfacearea of at least about 100 cm² and, in particular, a surface area ofabout 140 cm².

At least one aspect of the present technology provides a system forcontrolling core body temperature of a subject, comprising a heattransfer tube insertable within the esophagus of the subject; anexternal heat exchanger containing a heat transfer fluid; a pump forflowing the heat transfer fluid through a circuit within the heattransfer tube; a heat transfer element in contact with the external heatexchanger; a sensor for detecting a parameter and generating a signalrepresentative of the parameter, wherein the signal is transmitted to amicroprocessor to control (i) the flow of heat transfer fluid within thecircuit or (ii) the temperature of the heat transfer fluid. The tube isconfigured to contact the epithelial lining of the subject's esophagus.The sensor can be a temperature sensor positioned distal to the heattransfer tube and configured to generate a signal representing the corebody temperature of the subject. The microprocessor can receive a targettemperature input and responds to the signal from the temperature sensorwith a proportional integrated differential response to control the rateat which the subject approaches the target temperature. The sensor canbe a bubble detector and configured to generate a signal representingthe presence of air in the circuit. The heat transfer device can alsocomprise a hollow tube having a distal end configured to extend into thepatient's stomach. The heat transfer device can be capable of contactingsubstantially all of the patient's esophageal epithelium. The heattransfer device can comprise a semi-rigid material. The heat transferdevice can be capable of cooling at a rate of about 1.2° C./hr to about1.8° C./hr. The heat transfer device can be capable of cooling a mass ata rate of about 350 kJ/hr to about 530 kJ/hr, and, in particular, at arate of about 430 kJ/hr. The heat transfer device can include a heattransfer region with a surface area of at least about 100 cm² and, inparticular, a surface area of about 140 cm².

BRIEF DESCRIPTION OF SEVERAL VIEWS OF THE DRAWINGS

FIG. 1 is a schematic view of a heat transfer system according to anexemplary embodiment of the present technology.

FIG. 2 depicts a heat transfer device according to an exemplaryembodiment of the present technology.

FIG. 3 shows a schematic (FIG. 3A), top down (FIG. 3B), andcross-sectional (FIG. 3C) view of a heat transfer device according to anexemplary embodiment of the present technology.

FIG. 4 shows a schematic view of a proximal end of a heat transferdevice according to an exemplary embodiment of the present technology.

FIG. 5 shows a schematic view (FIG. 5A) and several cross-sectionalviews (FIGS. 5B-5F) of a distal end of a heat transfer device accordingto an exemplary embodiment of the present technology.

FIG. 6 is a schematic diagram of a distal end of a heat transfer deviceaccording to an exemplary embodiment of the present technology.

FIG. 7 is a graph depicting the cooling achieved with an exemplarycooling device according to an embodiment of the present technology.

FIG. 8 is a graphed comparison of the rate of cooling achieved by a heattransfer device of the present technology as compared to the rate ofcooling demonstrated in US Patent Application Publication 2004/0210281to Dzeng et al.

FIG. 9 is a graph showing the total amount of heat transferred duringthe warming and maintenance phase of the experiment.

DETAILED DESCRIPTION OF THE INVENTION

The present technology provides relatively non-invasive devices andmethods for heating or cooling a patient's entire body. The presenttechnology also provides devices and methods for treating ischemicconditions by inducing therapeutic hypothermia. Another aspect of thepresent technology provides devices and methods for inducing therapeutichypothermia through esophageal cooling. The present applicationdemonstrates that heat transfer devices and methods of the presenttechnology achieve unexpectedly-greater rates of temperature change ascompared to other devices and methods and, in particular, thosementioned in US Patent Application Publication 2004/0210281 to Dzeng etal.

The present technology provides devices and methods for treatingpatients suffering from various diseases and disorders by inducing mildtherapeutic hypothermia (target temperature: about 32° C. to about 34°C.) and maintaining normothermia (target temperature: about 37° C.). Inparticular, mild therapeutic hypothermia may be induced to treatpatients suffering from ischemia or conditions related to ischemia.Without being bound by any particular theory, it is believed thatseveral molecular and physiological responses associated with theischemia-reperfusion cascade, including, for example, glutamate release,stabilization of the blood-brain barrier, oxygen radical production,intracellular signal conduction, protein synthesis, ischemicdepolarization, reduced cerebral metabolism, membrane stabilization,inflammation, activation of protein kinases, cytoskeletal breakdown, andearly gene expression, are sensitive to intra- and post-ischemictemperature reductions. In particular, mild therapeutic hypothermia mayminimize the formation of several metabolic mediators such as freeradicals and suppress the inflammatory response associated withischemia-reperfusion. Moreover, with respect to neurological outcomes,mild therapeutic hypothermia may blunt the cerebral pro-inflammatoryresponse, decrease the production of excitatory mediators of braininjury, such as excitatory amino acids and monoamines, decrease thecerebral metabolic rate, and decrease intracranial pressure. On theother hand, inadvertent hypothermia during operative procedures canreduce platelet function, impair enzymes of the coagulation cascade,enhance anesthetic drug effects, contribute to coagulopathy, increasecardiac demand, and increase the incidence of surgical wound infections.

Certain embodiments of the present technology provide devices andmethods for inducing mild therapeutic hypothermia to treat individualswho have experienced myocardial infarction, stroke, traumatic braininjury, ARDS, hemorrhagic shock, subarachnoid hemorrhage (“SAH”),including non-traumatic aneurysmal SAH, neonatal encephalopathy,perinatal asphyxia (hypoxic ischemic encephalopathy), spinal cordinjury, meningitis, near hanging and near drowning. Without being boundby any particular theory, it is believed that mild therapeutichypothermia may prevent, reduce, or ameliorate neurological, or other,damage associated with the above-mentioned conditions. Additionalembodiments of the present technology provide devices and methods forinducing mild therapeutic hypothermia to treat individuals who haveexperienced metabolic acidosis, pancreatitis, malignant hyperthermia,liver failure and hepatic encephalopathy. Additional embodiments of thepresent technology provide devices and methods for controlling patienttemperature during any general surgical procedure. As used herein, theterm “controlling patient temperature” refers to a patient's core bodytemperature and includes lowering core body temperature, maintainingcore body temperature, raising core body temperature, inducinghypothermia, maintaining normothermia, and inducing hyperthermia.

Certain embodiments of the present technology provide for controllingpatient temperature through esophageal warming or cooling. As anexample, a heat transfer agent may be circulated through a heat transferdevice positioned in the patient's esophagus. In certain embodiments,the heat transfer portion of the device is confined to the patient'sesophagus. In certain embodiments, the heat transfer device is incontact with substantially all of the epithelial surface of thepatient's esophagus. The heat transfer device may include a balloon orpartially inflatable lumen. Alternatively, in certain embodiments of thepresent invention, the heat transfer portion of the heat transfer devicedoes not include a balloon or partially inflatable lumen.

In operation, heat can be transferred to the esophagus from the heattransfer agent, resulting in an increase in the temperature of theesophagus, as well as adjacent organs or structures, including theaorta, right atrium, vena cavae, and azygos veins, and ultimately,systemic normothermia, or heat can be transferred from the esophagus tothe heat transfer agent, resulting in a decrease in the temperature ofthe esophagus, as well as adjacent organs or structures, including theaorta, right atrium, vena cavae, and azygos veins, and ultimately,systemic hypothermia.

Certain other embodiments of the present technology provide forcontrolling patient temperature through esophago-gastric heat transfer.As an example, a heat exchange medium may be circulated through a heattransfer device of sufficient length such the heat transfer portion ofthe device extends from the patient's esophagus to the patient'sstomach. In certain embodiments, the heat transfer device is in contactwith substantially all of the epithelial surface of the patient'sesophagus. The heat transfer device may include a balloon or partiallyinflatable lumen. Alternatively, in certain embodiments of the presentinvention, the heat transfer portion of the device does not include aballoon or partially inflatable lumen. Employing such anesophago-gastric temperature control device to modulate patienttemperature provides increased surface area for heat transfer andthereby results in more efficient and more rapid temperature management.

Certain embodiments of the present technology provide for inducing mildtherapeutic hypothermia by, for example, esophageal cooling, to treatindividuals who have experienced cardiac arrest, includingcocaine-induced cardiac arrest, traumatic cardiac arrest, and cardiacarrest due to non-coronary causes.

Still other embodiments of the present technology provide forcontrolling patient temperature through cooling or warming of apatient's bladder, colon, rectum, or other anatomical structure. As anexample, a heat exchange medium may be circulated through a heattransfer device positioned in the patient's bladder, colon, rectum, orother anatomical structure.

Certain embodiments of the present technology provides for a heattransfer system for heating or cooling a patient. The heat transfersystem may include a heat transfer device, a heat exchanger, a heattransfer medium, and a network of tubular structures for circulating theheat transfer medium between the heat transfer device and the heatexchanger. In other embodiments, the heat transfer system includes aheat transfer device, a chiller, a coolant and a network of tubularstructures for circulating the coolant between the heat transfer deviceand the chiller. In still other embodiments, the heat transfer systemcan be used to cool and subsequently re-warm the patient, as well asmaintain the patient at a predetermined maintenance temperature.

In certain embodiments of the present technology, the heat transferdevice comprises a distal end, a proximal end, and one or more lengthsof tubing extending therebetween. The proximal end of the heat transferdevice includes an input port for receiving a heat transfer medium fromthe heat exchanger and an output port allowing the heat transfer mediumto return to the heat exchanger. The tubing extending from approximatelythe proximal end of the heat transfer device to approximately the distalend of the heat transfer device may include a heat transfer mediumsupply tube and a heat transfer medium return tube. The heat transfermedium supply tube and heat transfer medium return tube may be arranged,for example, in parallel or concentrically. The lumens of the heattransfer medium supply tube and heat transfer medium return tube may bein fluid communication such that the heat transfer medium may flow alonga fluid path defined by the lumens of the heat transfer medium supplytube and heat transfer medium return tube.

The thickness of the walls of the heat transfer medium supply tubeand/or heat transfer medium return tube contributes to the heat transferresistance of the device. Thus, in certain embodiments, it is preferablefor the heat transfer medium supply tube and/or heat transfer mediumreturn tube to have thin walls. For example, the wall of the heattransfer medium supply tube and/or heat transfer medium return tube maybe less than about 1 millimeter. Alternatively, the wall of the heattransfer medium supply tube and/or heat transfer medium return tube maybe less than about 0.01 millimeter. In some embodiments, the wall of theheat transfer medium supply tube and/or heat transfer medium return tubemay be less than about 0.008 millimeters. As will be appreciated by oneof skill in the art, the thickness of the walls of the heat transfermedium supply tube and/or heat transfer medium return tube may bemodified in increments of about 0.001 millimeters, about 0.01millimeters, or about 0.1 millimeters, for example.

The manufacture of heat transfer devices of the present technology isrelatively inexpensive. For example, an esophageal heat transfer devicecan be constructed using an elastomer such as biomedical grade extrudedsilicone rubber, and an adhesive. Commercially available elastomers andadhesives include, for example, Dow Corning Q7 4765 silicone and NusilMed2-4213. The low cost and ease of use of such materials is expected tolead to widespread adoption of the esophageal heat transfer devices ofthe present technology.

In certain embodiments, the heat transfer device, including, forexample, the supply tube, may comprise a semi-rigid material, such as asemi-rigid plastic, including ethylene tetrafluoroethylene (ETFE),polytetrafluoroethylene (PTFE), perfluoroalkoxy (PFA), and fluorinatedethylene propylene (FEP), or a semi-rigid elastomer, such as silicone. Aheat transfer device comprising a supply tube constructed of asemi-rigid material is easier to place into a patient's esophagus than,for example, a flexible, balloon-type device. In particular, a heattransfer device comprising a flexible material, such as a balloon,requires a delivery device, such as a catheter, guide wire, or sleeve,to direct the heat transfer device into the patient's esophagus.Moreover, flexible, expandable material like a balloon is susceptible tofailures, such as bursting, splitting, or puncturing. Use of asemi-rigid material in the construction of a heat transfer device,reduces the points of failure associated with balloon-type device.

In certain embodiments a rigid sleeve may be employed to guide the heattransfer device during placement into a patient. The rigid sleeve mayhave a section cut-out such that the sleeve comprises approximately asemi-circle in cross section. The sleeve may be removed by sliding itproximally off the heat transfer device. Such a sleeve has certainbenefits over a centrally placed guide wire, including a reduced rate ofcomplications from using a guide wire, such as loss of the guide wireinto the body cavity and damage caused by the guide wire itself.

An esophageal heat transfer device of the present technology isportable, relatively easy to use, and can be inserted into a patient'sesophagus by a single health care provider, including a nurse, certifiedfirst responder, paramedic, emergency medical technician, or otherpre-hospital or in-hospital care provider. An esophageal heat transferdevice of the present technology possesses advantages over devices thatrequire multiple people and/or a person trained in advanced medicalcare. In addition, in a surgical setting, for example, an esophagealheat transfer device of the present technology possesses advantages overother temperature management modalities in that less personnel andattention is required to insert, employ, and/or monitor an esophagealheat transfer device.

For example, users of a balloon-type device must guard against over- orunder-inflation of the balloon. Over-inflation can lead to undesiredoutcomes, including pressure necrosis. Under-inflation can reduce theability of he device to transfer heat to/from the patient. The use of aballoon-type heat transfer devices also may require the use of apressure monitor to monitor the inflation pressure. Even when used inconjunction with a pressure monitor, it may not be able to achieve theproper inflation of the balloon.

The heat transfer device may be, for example, a pharyngeo-esophagealheat transfer device, an esophageal heat transfer device, anesophago-gastric heat transfer device, or a pharyngeo-esophago-gastricheat transfer device. For example, an esophageal heat transfer devicemay include a heat transfer region of about twenty (20) centimeters.Alternatively, an esophago-gastric heat transfer device may include aheat transfer region of about forty (40) centimeters. As yet anotheralternative, a pharyngeo-esophago-gastric heat transfer device mayinclude a heat transfer region of about forty-five (45) to about fifty(50) centimeters. Heat transfer devices of the present technology caninclude heat transfer regions of about 22, about 24, about 26, about 28,about 30, about 32, about 34, about 36, about 38, about 40, about 42,about 44, about 46, about 48, about 50, about 52, about 54, about 56,about 58, about 60, about 62, about 64 about 66, about 68 or about 70centimeters.

Heat transfer devices of the present technology can have a heat transferregion having a diameter of, for example, about 1.0 to about 2.0centimeters. The diameter of the heat transfer region can be about 1.1,about 1.2, about 1.3, about 1.4, about 1.5, about 1.6, about 1.7, about1.8, or about 1.9 centimeters. In certain embodiments, a heat transferregion of a heat transfer device of the present technology has a lengthof about 32 centimeters and a diameter of about 1.4 centimeters, givinga surface area of about 140 cm².

Increasing the length and/or circumference of the heat transfer regionof the device, and therefore the surface area of the heat transferregion, improves the speed and efficiency at which the patient is cooledor heated (or re-warmed). In certain embodiments the heat transferregion can be about 15 in², about 20 in², about 25 in², 30 in², about 35in², about 40 in², about 45 in², about 50 cm², about 60 cm², about 70cm², about 80 cm², about 90 cm², about 100 cm², about 110 cm², about 120cm², about 130 cm², about 140 cm², about 150 cm², about 160 cm², about170 cm², about 180 cm², about 190 cm², about 200 cm², about 210 cm²,about 220 cm², about 230 cm², about 240 cm², about 250 cm², about 260cm², about 270 cm², about 280 cm², about 290 cm², about 300 cm², about310 cm², about 320 cm², about 330 cm², about 340 cm², or about 350 cm².In certain embodiments, a heat transfer region can contact substantiallyall of the epithelial surface of a subject's esophagus.

The heat transfer device may be adapted to permit gastric access to thepatient's health care provider. The heat transfer device mayincorporate, for example, a gastric tube or gastric probe. The gastrictube or gastric probe may run parallel to the heat transfer mediumsupply tube and the heat transfer medium return tube. Alternatively, thegastric tube, the gastric probe, or both may be in a concentricarrangement with at least one of the heat transfer medium supply tube orthe heat transfer medium return tube. The gastric probe may be, forexample, a temperature probe.

Another embodiment of the present technology provides for a multi-lumenheat transfer device for inducing mild therapeutic hypothermia. The heattransfer device may include one or more lumens that provide a fluid pathfor circulation of a coolant. For example, the heat transfer device mayinclude a coolant supply tube and a coolant return tube. The lumens ofthe coolant supply tube and coolant return tube may be in fluidcommunication with each other thereby defining a fluid path for coolantflow. The coolant supply tube and coolant return tube may be arranged,for example, in parallel or concentrically.

Another embodiment of the present technology provides for a multi-lumenheat transfer device for controlling patient temperature. The heattransfer device may include one or more lumens that provide a fluid pathfor circulation of a heat transfer medium. For example, the heattransfer device may include a medium supply tube and a medium returntube. The lumens of the medium supply tube and medium return tube may bein fluid communication with each other thereby defining a fluid path formedium flow. The medium supply tube and medium return tube may bearranged, for example, in parallel or concentrically.

Certain embodiments of the present technology may utilize a controllersuch as that described in US20070203552 (Machold). In particular, acontroller may employ a cascading proportional integrated differential(PID) control scheme. In such a scheme, a control system is providedthat may be divided into two sections: (a) a Bulk PID control sectionwhich takes input from the health care provider or other user, such astarget temperature, and input from the sensors on the patientrepresenting patient temperature, and calculates an intermediate setpoint temperature (SP1) and an output signal to the Heat Transfer FluidPID control; and (b) the Heat Transfer Fluid PID control, that receivesinput from the Bulk PID control section and from a sensor representingthe temperature of a heat transfer fluid, and generates a signal thatcontrols the temperature of the heat exchanger by, for example, varyingthe power input to the heat exchanger.

The heat transfer fluid circulates in heat exchanger, so the HeatTransfer Fluid PID essentially controls the temperature of the heattransfer fluid. In this way, the control scheme is able to automaticallyachieve a specified target based on input from sensors placed on thepatient and the logic built into the controller. Additionally, thisscheme allows the unit to automatically alter the patient temperaturevery gradually the last few tenths of a degree to achieve the targettemperature very gently and avoid overshoot or dramatic, and potentiallydamaging, swings in the electronic power to the heat exchanger. Once thetarget temperature is achieved, the system continues to operateautomatically to add or remove heat at precisely the rate necessary tomaintain the patient at the target temperature.

In general, the controller can include a controlled variable, such aspump output or power input to the heat exchanger. A detecting unit orsensor can act as a feedback device for detecting a parameter, such aspatient temperature or the presence of air in a line, and outputting afeedback signal relative to the control variable. The control unitperforms a PID operation, in which the controlled variable is adjustedaccording to the comparison between the feedback signal and apredetermined target value.

As an example, the feed back signal T can represent patient temperatureand the predetermined target value T_(Targ) can represent a targettemperature set by a health care professional. When the feedback signalT is larger than the target value T_(Targ), it means that the patient'stemperature is too high. Accordingly, the controller, for example,increases or decreases pump output or power input to the heat exchangerin order to change the temperature and/or flow rate of the heat exchangemedium. When the feedback signal T is smaller than the target valueT_(Targ), it means that the patient's temperature is too low.Accordingly, the controller, for example, increases or decreases pumpoutput or power input to the heat exchanger in order to change thetemperature and/or flow rate of the heat exchange medium.

Certain embodiments of the present technology provide an unexpectedlysuperior rate of temperature change relative to other devices andmethods. The present methods and devices can provide a rate of coolingof about 0.5° C./hour to about 2.2° C./hour in a large animal model ofsimilar size to an average adult human. Present methods and devices arecapable of demonstrating a total heat extraction capability of about 250kJ/hour to about 750 kJ/hour. For example, the present methods anddevices can provide a rate of cooling of about 1.2° C./hour to about1.8° C./hour in a large animal model of similar size to an average adulthuman, which demonstrates a total heat extraction capability of about350 kJ/hour to about 530 kJ/hour. Methods and devices of the presenttechnology can provide a rate of cooling of about 1.3, about 1.4, about1.5, about 1.6, and about 1.7° C./hour. Methods and devices of thepresent technology are capable of demonstrating a total heat extractioncapability of about 350, about 360, about 370, about 380, about 390about 400, about 410, about 420, about 430, about 440, about 450, about460, about 470, about 480, about 490, about 500, about 510, and about520 kJ/hour.

While not wishing to be bound by any particular theory, it is thoughtthat the methods and devices of the present technology transfer moreheat per unit time than other devices. For example, heat transferdevices of the present technology include heat transfer regions that,for example, extend to substantially the entire length and/orcircumference of the patient's esophagus, providing increased contactsurface between the heat transfer region of the heat transfer device andpatient anatomy including, the esophageal epithelium and the vasculaturethat surrounds the esophagus. Heat transfer devices of the presenttechnology additionally enable reduction of gastric pressure throughgastric ventilation, thereby reducing the possibility of ballooning anddistention of the esophageal mucosa away from contact with theesophageal mucosa, and further enhancing heat transfer across theesophageal mucosa. In addition, materials for constructing the heattransfer devices of the present technology include those with superiorheat transfer characteristics. Heat transfer devices of the presenttechnology can be manufactured with thinner wall thicknesses, furtherreducing the heat transfer resistance across the device and increasingthe effectiveness of heat extraction from, or heat addition to, thepatient.

The presently described technology now will be described with respect tothe appended figures; however, the scope of the present technology isnot intended to be limited thereby. It is to be understood that thescope of the present technology is not to be limited to the specificembodiments described herein. The technology may be practiced other thanas particularly described and still be within the scope of the claims.

FIG. 1 is a schematic view of a heat transfer system 100 according to anembodiment of the present technology. The heat transfer system 100includes a heat transfer device 102, a heat exchanger 104, a heattransfer medium 106, and a network of tubular structures 108 forcirculating the heat transfer medium 106 between the heat transferdevice 102 and the heat exchanger 104.

The heat exchanger 104 is configured to heat or chill the heat transfermedium 106. The heat exchanger 104 may be any of a variety ofconventionally designed heat exchanger 104 s. For example the heatexchanger 104 may be a standard chiller, such as an RF-25 RecirculatingChiller manufactured by New Brunswick Scientific. The heat transfermedium 106 may be a gas, such as, for example, nitrous oxide, Freon,carbon dioxide, or nitrogen. Alternatively, the heat transfer medium 106may be a liquid, such as, for example, water, saline, propylene glycol,ethylene glycol, or mixtures thereof. In other embodiments, the heattransfer medium 106 may be a slurry, such as, for example, a mixture ofice and salt. In still other embodiments, the heat transfer medium 106may be a gel, such as, for example, a refrigerant gel. Alternatively,the heat transfer medium 106 may be a solid, such as, for example, iceor a heat conducting metal. In other embodiments, the heat transfermedium 106 may be formed, for example, by mixing a powder with a liquid.Thus, it should be understood that combinations and/or mixtures of theabove-mentioned media may be employed to achieve a heat transfer medium106 according to the present technology.

The network of tubular structures 108 for circulating the heat transfermedium 106 may include an external supply tube 110 and an externalreturn tube 112. The external supply tube 110 defines an external supplylumen 114 providing a fluid path for flow of the heat transfer medium106 from the heat exchanger 104 to the heat transfer device 102. Theexternal return tube 112 defines an external return lumen 116 providinga fluid path for flow of the heat transfer medium 106 from the heattransfer device 102 to the heat exchanger 104. A pump 118 may beemployed to circulate the heat transfer medium 106 through the networkof tubular structures 108, and the flow rate of the medium, and, hencethe heat transfer capabilities of the device, can be regulated byadjusting the pumping rate.

The heat transfer device 102 is adapted for placement within ananatomical structure of a mammalian patient. The heat transfer device102 has a proximal and a distal end. The distal end of the heat transferdevice 102 may be configured for insertion into a body orifice. Forexample, the distal end of the heat transfer device 102 may beconfigured for insertion into the nostrils, mouth, anus, or urethra of apatient. When properly inserted, the distal end of the heat transferdevice 102 may be ultimately positioned in the esophagus, rectum, colon,bladder, or other anatomical structure. The proximal end of the heattransfer device 102 includes an input port 120 and an output port 122.The input port 120 and output port 122 are connected to the network oftubular structures 108 for circulating the heat transfer medium 106. Forexample, the input port 120 may be connected to the external supply tube110 and the output port 122 may be connected to the external return tube112. Thus, in certain embodiments, the heat exchanger 104 may be influid communication with the heat transfer device 102 via the network oftubular structures 108.

In operation, the heat transfer device 102 is positioned into ananatomical structure, such as the esophagus. The heat exchanger 104 isused to heat or chill the heat transfer medium 106 that is supplied tothe heat transfer device 102 via the external supply tube 110. The heattransfer medium 106 flows through the external supply tube 110 andenters the heat transfer device 102 through the input port 120. The heattransfer medium 106 circulates through the heat transfer device 102 andexits the heat transfer device 102 through the output port 122, andreturns to the heat exchanger 104 via the external return tube 112.Raising or lowering the temperature of the heat transfer medium 106alters the body temperature of the patient.

The heat transfer system 100 may further incorporate a device thatmeasures a physiological parameter such as temperature, pressure, orelectromagnetic fluctuations. For example, the heat transfer system 100may include one or more thermometers 124, each with one or moretemperature probes 126, for measuring the ambient temperature, patienttemperature, or heat transfer medium 106 temperature. The thermometersmay be separate devices or integrated with the heat transfer system 100.

FIG. 2 depicts a heat transfer device 200 according to an embodiment ofthe present technology. For purposes of further elucidating thisembodiment, the heat exchanger will be referred to as a chiller (notshown) and the heat transfer medium will be referred to as a coolant.However, it should be understood that any suitable heat exchanger andany suitable heat transfer medium may be employed with the heat transferdevice depicted in FIG. 2.

The heat transfer device 200 comprises a distal end 202, a proximal end204, and a length of flexible tubing 206 extending therebetween. Theproximal end 202 includes an input port 208 for receiving coolant fromthe chiller and an output port 210 allowing coolant to return to thechiller.

The input port 208 comprises a standard plumbing tee fitting 212.Alternatively, any fitting with two or more open ends, such as a wyefitting may be employed. The fitting may be composed of any suitablematerial, including, for example metal, such as, copper or iron; metalalloy, such as steel or brass; or plastic, such as, polyvinyl chloride(“PVC”) or polyethylene (“PE”). A brass plug 214 is affixed to theproximal open end of the tee fitting 212. Alternatively, standard caps,such as metal or plastic caps, may be affixed to the proximal open endof the fitting. The plug 214 includes an opening to allow for tubingclearance. The plug 214 is affixed to the fitting with chemical sealant216, such as, for example, Room-Temperature Vulcanization (“RTV”)Silicone Sealant. In other embodiments, the input port 208 may bemanufactured in a way that eliminates the need for affixed end caps,such as, for example, by extrusion.

The output port 210 comprises a standard plumbing tee fitting 212.Alternatively, any fitting with two or more open ends, such as a wyefitting may be employed. The fitting may be composed of any suitablematerial, including, for example metal, such as, copper or iron; metalalloy, such as steel or brass; or plastic, such as, PVC or PE. Brassplugs 214 are affixed to the proximal open end and distal open end ofthe tee fitting. Alternatively, standard caps, such as metal, metalalloy, or plastic caps, may be affixed to the open ends of the fitting.Each plug 214 may include an opening to allow for tubing clearance. Theplugs 214 are affixed to the fitting with chemical sealant 216, such as,for example, RTV Silicone Sealant. In other embodiments, the output port210 may be manufactured in a way that eliminates the need for affixedend caps, such as, for example, by extrusion.

The length of tubing 206 extending between the proximal end 204 anddistal end 202 of the heat transfer device 200 is a coolant supply tube218. The coolant supply tube 218 may be composed of clear vinyl.Alternatively, the coolant supply tube 218 may be composed of othersuitable materials, such as, for example, flexible medical gradetransparent PVC. The dimensions of the coolant supply tube 218 may beapproximately 0.625″ outside diameter (“OD”)×0.500″ inside diameter(“ID”). The coolant supply tube 218 is affixed to the input port 208with chemical sealant 216, such as, for example, RTV Silicone Sealant.The coolant supply tube 218 extends from the input port 208 to thedistal end 202 of the heat transfer device 200. The length of thecoolant supply tube 218 may be about eighteen (18) to about fifty-two(52) centimeters. In certain embodiments, the length of the coolantsupply tube 218 may be from about eighteen (18) to about twenty-two (22)centimeters. In certain embodiments, the length of the coolant supplytube 218 may be from about thirty (30) to about forty-two (42)centimeters. In other embodiments, the length of the coolant supply tube218 may be from about forty-five (45) to about fifty-two (52)centimeters. The length of the coolant supply tube 218 can be aboutthirty-two (32) centimeters.

The distal end 202 of the heat transfer device 200 includes an end cap220. The end cap 220 may be composed of any suitable material,including, for example, metal, such as, copper or iron; metal alloy,such as steel or brass; or plastic, such as, PVC or PE. The end cap 220is affixed to the coolant supply tube with chemical sealant 216, suchas, for example, RTV Silicone Sealant.

A coolant return tube 222 may be positioned within the coolant supplytube 218. The coolant return tube 222 may be composed of clear vinyl.Alternatively, the coolant return tube 222 may be composed of othersuitable materials, such as, for example, flexible medical gradetransparent PVC. The outside diameter of the coolant return tube 222 issmaller than the inside diameter of the coolant supply tube 218. Forexample, the dimensions of the coolant return tube 222 may beapproximately 0.437″ outside diameter (“OD”)×0.312″ inside diameter(“ID”). The coolant return tube 222 may be affixed to one or both of theinput port 208 or output port 210 with chemical sealant 216, such as,for example, RTV Silicone Sealant.

The coolant return tube 222 does not extend to the end cap 220 at thedistal end 202 of the heat transfer device 200. Thus, the lumen of thecoolant supply tube 224 and the lumen of the coolant return tube 226 maybe in fluid communication with each other, thereby defining a fluid pathfor coolant flow.

In operation, the coolant enters the input port 208 and flows throughthe lumen of the coolant supply tube 224 to the distal end 202 of theheat transfer device 200, which may be positioned in, for example, theesophagus of a patient. The coolant then flows through the lumen of thecoolant return tube 226 to the output port 210. In operation, heat istransferred from, for example, the esophagus to the coolant, resultingin a decrease in the temperature of the esophagus, as well as adjacentorgans, and ultimately, systemic hypothermia.

In certain embodiments, additives with high heat transfer coefficient,such as copper, for example, may be added to the material used formanufacture of the coolant supply tube 218 or the coolant return tube222. In one embodiment, lengths of wire, for example, running linearlyor spiraling along the length of the tube may be included. In otherembodiments, particulate matter with a high heat transfer coefficientmay be mixed in to the material used for manufacture of the coolantsupply tube 218 or the coolant return tube 222 (for example, vinyl orPVC) before or during extrusion.

In certain embodiments, the walls of the coolant supply tube 218 and/orcoolant return tube 222 may be relatively thin. For example, the wall ofthe coolant supply tube 218 may be less than about 1 millimeter.Alternatively, the wall of the coolant supply tube 218 may be less thanabout 0.01 millimeter. In some embodiments, the wall of the coolantsupply tube 218 may be less than about 0.008 millimeters. As will beappreciated by one of skill in the art, the thickness of the walls ofthe heat transfer medium supply tube and/or heat transfer medium returntube may be modified in increments of about 0.001 millimeters, about0.01 millimeters, or about 0.1 millimeters, for example.

Optionally, the heat transfer device 200 may include a gastric tube 228,to allow for gastric access and, for example, gastric suctioning as wellas gastric lavage for diagnosis and/or therapeutic purposes, if sodesired. The gastric tube 228 may be composed of clear vinyl.Alternatively, the gastric tube 228 may be composed of other suitablematerials, such as, for example, flexible medical grade transparent PVC.The outside diameter of the gastric tube 228 is smaller than the insidediameter of the coolant return tube 222. For example, the dimensions ofthe gastric tube 228 may be approximately 0.250″ outside diameter(“OD”)×0.170″ inside diameter (“ID”). The gastric tube 228 may beaffixed to the most proximal port, either the input port 208 or theoutput port 210, with chemical sealant 216, such as, for example, RTVSilicone Sealant. The gastric tube 228 may allow the patient's healthcare provider to insert, for example, a nasogastric tube that allows forsuctioning of the gastric contents. Alternatively, the gastric tube 228may allow the patient's health care provider to insert, for example, agastric temperature probe (not shown).

Optionally, an antibiotic or antibacterial coating may be applied toportions of the coolant supply tube 218, the coolant return tube 222, orthe gastric tube 228. Particularly, an antibiotic or antibacterialcoating may be applied to portions of the tubes that, upon insertion toa patient, may contact, for example, a mucosal lining of the patient.For example, topical antibiotics, such as tobramycin, colistin,amphotericin B, or combinations thereof, may be applied to the tubes.Incorporation of an antibiotic or antibacterial coating may allowselective decontamination of the digestive tract (“SDD”), which mayfurther improve outcome.

As another alternative, all or part of the heat transfer device 200 canbe manufactured by, for example, extrusion. Employing such amanufacturing modality would eliminate the need to seal junctions oraffix end caps and reduce the points at which leaks may occur.

FIG. 3 depicts a heat transfer device 300 according to an embodiment ofthe present technology. The heat transfer device 300 comprises aproximal end 302, a distal end 306, and a length of flexible tubing 304extending therebetween.

All or part of the heat transfer device 300 can be manufactured by, forexample, extrusion. Employing such a manufacturing modality wouldeliminate the need to seal junctions or affix end caps and reduce thepoints at which leaks may occur. Alternatively, or additionally, a fastcuring adhesive, such as RTV silicone sealant or temperature-curablesealant can be used to seal junctions and/or bond tubing together. Theheat transfer device 300 can be constructed using a biocompatibleelastomer and/or plastic, and, optionally, adhesive. For example,biomedical grade extruded silicone rubber such as Dow Corning Q7 4765silicone, and an adhesive such as Nusil Med2-4213 can be used tomanufacture heat transfer device 300.

FIG. 3A shows a schematic view of the exterior of heat transfer device300. The heat transfer device 300 includes an input port 308, a heattransfer medium supply tube 310, a heat transfer medium return tube 312,and an output port 314. The heat transfer device also includes a centraltube 316 that, for example, allows for gastric access. The central tube316 is in a concentric arrangement with the heat transfer medium supplytube 310 or the heat transfer medium return tube 312 (see FIG. 3B). Thecentral tube lumen 318 provides the health care professional with accessto, for example, the patient's stomach while the heat transfer device ispositioned within the patient's esophagus.

FIG. 3C is a cross-sectional view along the line 3C, which is identifiedin FIG. 3B.

The outermost tube is the heat transfer medium supply tube 310. The heattransfer medium supply tube 310 extends from about the input port 308 toabout the distal end 306 of the heat transfer device 300. The length ofthe heat transfer medium supply tube 310 can be about eighteen (18) toabout seventy-five (75) centimeters. In a particular embodiment, thelength of the heat transfer medium supply tube 310 is about thirty-two(32) centimeters. The outside diameter of the heat transfer mediumsupply tube 310 can be, for example, about 1.0 to about 2.0 centimeters.In a particular embodiment, the outside diameter of the heat transfermedium supply tube 310 is about 1.4 centimeters.

Upon insertion into, for example, the esophagus of a patient, the wallof the heat transfer medium supply tube 310 can be in direct contactwith the patient's esophagus. As noted above, the length and/orcircumference of the heat transfer medium supply tube 310, and thereforethe surface area of heat transfer medium supply tube 310, can vary.Increasing the area of contact between the heat transfer device 300 andthe patient's esophagus improves the speed and efficiency at which thepatient is cooled or heated (or re-warmed). In certain embodiments thesurface area of the heat transfer medium supply tube 310 can be fromabout 50 cm² to about 350 cm². In a particular embodiment, the surfacearea of the heat transfer region of the heat transfer medium supply tube310 can be about 140 cm². In certain embodiments, the heat transfermedium supply tube 310 can contact substantially all of the epithelialsurface of a patient's esophagus.

Positioned within the heat transfer medium supply tube 310 is the heattransfer medium return tube 312. The outside diameter of the heattransfer medium return tube 312 is smaller than the inside diameter ofthe heat transfer medium supply tube 310. The heat transfer mediumreturn tube 312 does not extend to the distal end of the heat transfermedium supply tube 310. Thus, the heat transfer medium supply tube lumen320 and the heat transfer medium return tube lumen 322 are in fluidcommunication with each other, thereby defining a fluid path for theflow of the heat transfer medium.

Positioned within the heat transfer medium return tube is the centraltube 316. The outside diameter of the central tube 316 is smaller thanthe inside diameter of the heat transfer medium return tube 312. Thecentral tube 316 can be, for example, a gastric tube, to allow forgastric access. The central tube 316 allows a health care professionalto insert, for example, a nasogastric tube that allows for suctioning ofthe gastric contents. Alternatively, the central tube 316 allows ahealth care professional to insert, for example, a gastric temperatureprobe.

The distal end of the heat transfer medium supply tube 310 can be sealedwith an end cap 324. The end cap 324 can be constructed from, forexample, silicone. The end cap 324 can include a hole or otherpassageway through which central tube 316 can pass. Likewise, theproximal end of the heat transfer medium return tube 312 can be sealedwith an end cap 326. The end cap 326 can be constructed from, forexample, silicone. The end cap 326 can include a hole or otherpassageway through which central tube 316 can pass. Junctions betweenthe various components and tubes can be sealed with a sealant 328, suchas Nusil Med2-4213.

FIG. 4 shows several views of a proximal end of a heat transfer deviceaccording to the present technology.

The heat transfer device comprises at least two concentrically arrangedtubes, such as a heat transfer supply tube 402 and a heat transferreturn tube 404, forming a multi-lumen heat transfer device having agenerally coaxial lumen configuration. The proximal ends of each of theheat transfer supply tube 402 and the heat transfer return tube 404 canbe sealed with end caps (not shown). The heat transfer device,optionally, includes a first central tube 410 and/or a second centraltube 412. For example, the heat transfer device can comprise one or moregastric tubes.

The heat transfer supply tube lumen 406 is of sufficient diameter toallow passage of the heat transfer return tube 404. Likewise, the heattransfer return tube lumen 408 may be of sufficient diameter to allowpassage of the first central tube 410 and/or the second central tube412. The first central tube 410 and the second central tube 412 can be,for example gastric tubes that provide access to the patient's stomachand allow for suctioning of gastric contents and/or placement of agastric temperature probe. The end cap (not shown) of the heat transferreturn tube 404 can include a hole or other passageway through whichcentral tubes 410 and 412 pass.

The heat transfer supply tube 402 may be coupled to an input port 414.The input port 414 may be coupled to an external supply tube (not shown)equipped with standard connectors for interface with a chiller and/orwarming device. The heat transfer return tube 404 may be coupled to anoutput port 416. The output port 416 may be coupled to an externalreturn tube (not shown) equipped with standard connectors for interfacewith the chiller and/or warming device.

FIG. 5 shows schematic and cross-section views of a distal end of a heattransfer device according to the present technology.

The heat transfer device as depicted in FIG. 5A comprises at least twoconcentrically arranged tubes, such as a heat transfer supply tube 502and a heat transfer return tube 504, to form a multi-lumen heat transferdevice having a generally coaxial lumen configuration. The distal end ofthe heat transfer supply tube 502 extends beyond the distal end of heattransfer return tube 504 such that the heat transfer supply tube 502 andheat transfer return tube 504 form a heat transfer flow path. The distalend of the heat transfer supply tube 502 can be rounded or otherwiseformed to facilitate insertion and positioning of the heat transferdevice in the patient's esophagus. The heat transfer device can alsocomprise a first central tube 506 and/or a second central tube 508. Thefirst central tube 506 and the second central tube 508 can be, forexample gastric tubes that provide access to the patient's stomach andallow for suctioning of gastric contents and/or placement of a gastrictemperature probe.

FIG. 5B is a cross-sectional view along the line 58, which is identifiedin FIG. 5A. The heat transfer supply tube 502 and the heat transferreturn tube 504 are arranged concentrically. The heat transfer returntube 504 is positioned within the heat transfer supply tube lumen 510.The first central tube 506 and the second central tube 508 arepositioned within the heat transfer return tube lumen 512. A health careprofessional can, for example, insert a gastric temperature probe (notshown) through the first central tube lumen 514 and/or the secondcentral tube lumen 516.

FIGS. 5C-5F show cross-sectional views of several alternativeconfigurations of a multi-lumen heat transfer device according to anembodiment of the present technology.

As shown in FIG. 5C, the heat transfer supply tube lumen 510 and theheat transfer return tube lumen 512 can be arranged in parallel to eachother. As shown in FIG. 5D, the first central tube lumen 514 and thesecond central tube lumen 516 can also be arranged in parallel to theheat transfer supply tube lumen 510 and the heat transfer return tubelumen 512. Alternatively and as shown in FIGS. 5E and 5F, the firstcentral tube lumen 514 and/or the second central tube lumen 516 can bepositioned between the heat transfer supply tube lumen 510 and the heattransfer return tube lumen 512. Optionally, a gastric tube or a gastricprobe can be inserted into a patient's stomach via the first centraltube lumen 514 and/or the second central tube lumen 516.

The esophageal heat transfer device shown in FIGS. 2-5 and furtherdiscussed herein above is merely exemplary and not meant to be limitingto the present technology. The heat transfer device of the presenttechnology may be configured for insertion into the nostrils, mouth,anus, or urethra of a patient. When properly inserted, the heat transferportion of the device may be ultimately positioned in the esophagus,stomach, rectum, colon, bladder, or other anatomical structure.

FIG. 6 depicts a schematic view of a distal end of a heat transferdevice according to an embodiment of the present technology.

In certain embodiments, an esophageal heat transfer device incorporatesa gastric tube 602. The gastric tube 602 may be the center tube of theconcentric arrangement of tubes and may comprise a generally hollow tubethat provides gastric access. For example, a tube that allows forsuctioning of the gastric contents may be inserted into the patient'sstomach via the gastric tube 602. In certain embodiments, the gastrictube 602 serves as a tube for suctioning stomach contents and the needto place a separate nasogastric tube is eliminated. As another example,a gastric temperature probe may be inserted via the gastric tube 602.

The gastric tube 602 may include several ports 604 that serve as smalltubular connections or passageways from the external environment (here,the patient's stomach) to gastric tube lumen 606. The ports 604 maycommunicate directly (and only) with the gastric tube lumen 606. Theports 604 may be positioned at the distal end of the heat transferdevice to provide additional communication portals between the patient'sstomach and the gastric tube 602. The ports 604 provide for additionalpassageways for gastric contents to flow from the patient's stomach outthrough the gastric tube lumen 606, thereby reducing the likelihood ofblockage of the single lumen from semi-solid stomach contents.

In other embodiments, an esophago-gastric heat transfer device comprisesconcentric tubes such that the center-most tube serves as a gastric tube602. In such an arrangement, the outermost tube can be, for example, aheat transfer medium supply tube 608. A heat transfer medium return tube610 can be positioned within the heat transfer medium supply tube 608.Likewise, the gastric tube 602 can be positioned within the heattransfer medium return tube 610.

As shown in FIG. 6, the heat transfer device may be an esophageal oresophago-gastric heat transfer device and comprise three concentricallyarranged tubes, including a heat transfer medium supply tube 608, a heattransfer medium return tube 610, and a gastric tube 602 to form amulti-lumen heat transfer device having a generally coaxial lumenconfiguration. The heat transfer portion of the heat transfer device maybe confined to the patient's esophagus, while the gastric tube 602extends into the patient's stomach. The heat transfer device may furtherinclude ports 604 along the side of the gastric tube 602. The distal endof the gastric tube 602 includes several ports along the side of thetube to provide access to the gastric tube lumen 606, thereby reducingthe likelihood of blockage of the single lumen from semi-solid stomachcontents. The addition of such ports 604 may improve and enhance theremoval of stomach contents, which, in turn, may improve contact betweengastric mucosa and the heat transfer device. Such improved contact mayenhance heat transfer between the heat transfer device and the gastricmucosa.

The configuration of the ports as shown in FIG. 6 is oval. However, theports can be, for example, circular, rectangular, or any other shapethat permits flow of gastric contents from the stomach to the gastrictube lumen 606.

In certain embodiments, the term “patient” refers to a mammal in need oftherapy for a condition, disease, or disorder or the symptoms associatedtherewith. The term “patient” includes dogs, cats, pigs, cows, sheep,goats, horses, rats, mice and humans. The term “patient” does notexclude an individual that is normal in all respects.

As used herein, the term “treating” refers to abrogating; preventing;substantially inhibiting, slowing or reversing the progression of;substantially ameliorating clinical and/or non-clinical symptoms of; orsubstantially preventing or delaying the appearance of clinical and/ornon-clinical symptoms of a disease, disorder or condition.

In the preceding paragraphs, use of the singular may include the pluralexcept where specifically indicated. As used herein, the words “a,”“an,” and “the” mean “one or more,” unless otherwise specified. Inaddition, where aspects of the present technology are described withreference to lists of alternatives, the technology includes anyindividual member or subgroup of the list of alternatives and anycombinations of one or more thereof.

The disclosures of all patents and publications, including publishedpatent applications, are hereby incorporated by reference in theirentireties to the same extent as if each patent and publication werespecifically and individually incorporated by reference.

It is to be understood that the scope of the present technology is notto be limited to the specific embodiments described above. The presenttechnology may be practiced other than as particularly described andstill be within the scope of the accompanying claims.

Likewise, the following examples are presented in order to more fullyillustrate the present technology. They should in no way be construed,however, as limiting the broad scope of the technology disclosed herein.

EXAMPLES Example 1 Cooling of a Model System

An experiment was conducted to quantify the approximate rate oftemperature reduction achievable by use of an exemplary embodiment ofthe present technology. Target temperature reduction is 4° C. Data werecollected and plotted on a common X-Y graph, as shown in FIG. 7.

The arrangement of equipment for this experiment is shown in FIG. 1. Abrief description of each piece of equipment is as follows:

-   -   1. The heat transfer device 102 was an exemplary embodiment of a        heat transfer device according to the present technology    -   2. An insulated container, 96 cm (I)×36 cm (w)×36 cm (h),        containing 88 kg water at the initial temperature shown in Table        1 represented the mass to be cooled.    -   3. A 110V electric pump, Little Giant Model PES-70 (4.4 L/min        free-flow) was used to circulate hot water within the insulated        container (2) to maintain homogeneous temperature of water        within this container.    -   4. The heat exchanger 104 comprised an insulated container, 51        cm (I)×28 cm (w)×34 cm (d), containing 40 kg ice water.    -   5. The pump 118 comprised a 110V electric pump, Little Giant        Model PES-70 (250 mL/min as installed) and was used to provide        circulation of coolant from the heat exchanger 104 through the        external supply tube 110, then through the heat transfer device        102, then through the external return tube 112, and back to the        heat exchanger 104.    -   6. The external supply tube 110 comprised a Watts clear vinyl        #SVKI10, ⅝″ (od)×½″ (id)×42″ (I), to carry coolant from the heat        exchanger 104 to the heat transfer device 102.    -   7. The external return tube 112 comprised a Watts clear vinyl        #SVKI10, ⅝″ (od)×½″ (id)×42″ (I), to carry coolant from heat        transfer device 102 to the heat exchanger 104.    -   8. A thermometer 124, such as a digital waterproof thermometer        including 2 remote probes 126, Taylor Model 1441, was used to        monitor:        -   a. coolant temperature (T₃ as shown in FIG. 1) near the            discharge of the external return tube 112 into the heat            exchanger 104;        -   b. ambient temperature (T₄ as shown in FIG. 1) within test            cell.    -   9. A thermometer 124, such as a digital waterproof thermometer        including 2 remote probes 126, Taylor Model 1441, was used to        monitor:        -   a. hot water temperature (T₁ as shown in FIG. 1) within            insulated container (2), at the end opposite circulation            pump (3).        -   b. hot water temperature (T₂ as shown in FIG. 1) within            insulated container (2), at the end nearest circulation pump            (3).

The body to be cooled in each iteration of this experiment was an 88-kgmass of water, which was held in an insulated container (2) measuring94×36×26 cm. This mass was chosen as it is representative of the bodymass of a typical adult male. Heat transfer to ambient air by freeconvection was through the 94×36 cm top surface of the body of water.Initial temperature of this mass of water for each iteration of theprocedure is shown in Table 1.

The coolant for each iteration of this experiment was a 30-kg mass ofwater containing an additional 10-kg of ice, which was held in aninsulated container. Ice was used to keep the temperature of the coolantnearly constant for the duration of each iteration of the experimentwithout the need for a powered chiller, and was replenished at the startof each iteration for which the conductive cooling mode was enabled.

There are two modes of temperature reduction to consider in thisexperiment. They are convective cooling to ambient air, and conductivecooling through the heat transfer device. To quantify the contributionof each mode to the total temperature reduction, a control case was runwith the conductive cooling mode disabled (no coolant circulated throughthe heat transfer device). The procedure was then run two additionaltimes with the conductive cooling mode enabled (the heat transfer devicewas submerged in the body of hot water, and coolant circulated throughit). The difference between temperature reduction rates, with andwithout conductive cooling enabled, is the temperature reduction ratedue to conductive cooling through the heat transfer device.

Summary of data for each iteration of the experiment is shown in Table 1below:

TABLE 1 Cooling Experiment Results 4° C. T_(init, avg) T_(amb, avg)T_(coolant, avg) drop time Iteration Description ° C. ° C. ° C. (hh:mm)1 Control case, 38.8 19.6 N/A 02:53 convection to ambient only 2Conductive 39.4 20.3 3.9 01:39 cooling enabled, Run #1 3 Conductive 38.120.4 3.5 01:38 cooling enabled, Run #2

In Table 1:

-   -   “T_(init,avg)” is the average initial temperature of the body to        be cooled, average of two readings    -   “T_(amb,avg)” is the average ambient temperature for the        duration of the iteration    -   “T_(coolant,avg)” is the average coolant temperature for the        duration of the iteration    -   “4° C. drop time” is the time required to achieve a 4° C.        reduction in average temperature of the body to be cooled.

Thus, conductive cooling through the exemplary heat transfer deviceemployed in this Example significantly decreases time to achieve a 4° C.temperature reduction.

Example 2 Operative Temperature Management

A heat transfer device according to the present technology was utilizedin an animal study as described below. The heat transfer region of theheat transfer device was approximately 70 centimeters in length (toaccommodate the length of the snout) and had a diameter of about 1.4centimeters, for a surface area of about 305 cm².

A large swine with a mass of 70 kg was chosen to best represent the sizeand average mass of a human patient. The swine was singly housed in anAssociation for the Assessment and Accreditation of Laboratory AnimalCare, International (AAALAC) accredited facility, with primaryenclosures as specified in the USDA Animal Welfare Act (9 CFR Parts 1, 2and 3) and as described in the Guide for the Care and Use of LaboratoryAnimals (National Academy Press, Washington D.C., 1996).

The swine was anesthetized with a pre-anesthetic mix ofTelozole/Xylazine, then provided with anesthesia via inhalational routewith isoflurane 2% after endotracheal intubation achieved with standardendotracheal intubation equipment and technique well known to thoseskilled in the art. Muscular paralysis was obtained with intravenousparalytic. Temperature was monitored continuously via rectalthermocouple probe placed after anesthesia and endotracheal intubation.

A commercially available thermal water bath and circulator (GaymarMeditherm MTA-5900) was utilized to provide a controlled-temperatureheat transfer medium to the heat transfer device. The specific heattransfer medium utilized was distilled water. Specifications of thecommercially available thermal water bath and circulator are as follows:

Dimensions: 94 cm H×35 cm W×48 cm D

Weight: 54.9 kg empty; 64.0 kg full

Material: Aluminum Shell, 16 Gauge Steel Chassis

Flow Rate: 1 liter per minute

Power: 220V, 240V, 50 Hz, 6 A

Temperature: Manual: 4 to 42° C., Automatic: 30 to 39° C.

Electrical Cord: 4.6 m detachable power cord

The heat transfer device was connected to the thermal water bath andcirculator, which was then powered on and allowed to equilibrate whilepreparing the swine.

After successful anesthesia, paralysis, and endotracheal intubation ofthe swine, a central semi-rigid stylet was placed into the heat transferdevice and the heat transfer device was lubricated with a biocompatiblelubricant.

The heat transfer device was then introduced into the esophagus of theswine using standard esophageal intubation technique well known to thoseskilled in the art. An external measurement of the distance fromoropharyngeal opening to xiphoid process served as an indicator to whichthe depth of the heat transfer device was inserted. Confirmation ofproper depth of insertion was obtained by successful aspiration ofgastric contents through the gastric lumen of the heat transfer device.

In order to demonstrate the capacity of the heat transfer device tosuccessfully warm a patient under hypothermic conditions typically foundin the operating room environment, the swine was cooled by setting thesupply temperature of the heat transfer medium to the low set point (4°C.) for a time sufficient to reduce the temperature of the swine to33.6° C.

Data from the cooling portion of the experiment are shown in Table 2. Ascan be seen in Table 2, a 1° C. reduction in core body temperature of a67.5 kg swine was achieved in about 40 minutes; a 2° C. reduction incore body temperature of a 67.5 kg swine was achieved in about 80minutes; a 3° C. reduction in core body temperature of a 67.5 kg swinewas achieved in about 125 minutes; and a 4° C. reduction in core bodytemperature of a 67.5 kg swine was achieved in about 175 minutes.

TABLE 2 Esophageal Cooling. Time (min) Rectal Temperature (° C.) 0 37.810 37.8 15 37.6 20 37.4 25 37.3 32 37.2 35 37 40 36.8 45 36.7 50 36.6 5536.4 60 36.3 65 36.1 70 36 75 35.9 80 35.7 85 35.6 90 35.5 95 35.4 10035.3 105 35.2 110 35.1 115 35 120 34.9 125 34.8 130 34.7 135 34.6 14034.5 145 34.4 150 34.4 155 34.3 160 34.2 165 34.1 170 33.9 175 33.8 18033.7 185 33.6

FIG. 8 shows a comparison of the rate of cooling achieved by a heattransfer device of the present technology as compared to the rate ofcooling demonstrated in US Patent Application Publication 2004/0210281to Dzeng et al. In order to make an accurate comparison, and to properlyaccount for the differences in mass between the two experiments, thetotal amount of heat extracted in each case is calculated in standardunits of Joules. Using a standard specific heat capacity of water(c_(p)=4.186 J/g C) to model the specific heat capacity of theexperimental animal, the heat extracted at each time point is calculatedas Q=m(ΔT)c_(p), where m is the mass of the experimental animal, and ΔTis the temperature difference obtained at each time point.

At the time point of one hour, the total heat extracted is 439 kJ in onehour (122 Watts) with a heat transfer device of the present technology,as compared to a total heat extraction of 260 kJ in one hour (72 Watts)achieved with the device mentioned by Dzeng et al. in US PatentApplication Publication 2004/0210281.

The results of the swine cooling experiment show that even in arelatively large animal, with correspondingly greater heat reservoircapacity, a significantly greater heat transfer rate is achievable witha heat transfer device of the present technology than with prior devicessuch as those mentioned by Dzeng et al. in US Patent ApplicationPublication 2004/0210281. From the data presented, the total heatextracted, and the consequent cooling achieved, can be seen to besignificantly greater with a heat transfer device of the presenttechnology as compared to the rate of heat transfer and cooling achievedwith prior devices such as those mentioned by Dzeng et al. in US PatentApplication Publication 2004/0210281. Thus, it was unexpectedly andsurprisingly observed that the cooling rate achieved with a heattransfer device of the present technology is significantly greater thanthat achieved with other devices and that the methods and devices of thepresent technology transfer more heat per unit time than other devices.Without wishing to be bound by any particular theory, it is thought thatthese unexpected findings can be attributed to, for example, one or moreof the following features of the heat transfer device: the increasedcontact surface between the heat transfer region of the heat transferdevice and the patient's anatomy; the reduction in heat transferresistance across the device achieved by manufacturing heat transferdevices of the present technology with thinner wall thicknesses; thesuperior heat transfer characteristics of the materials used toconstruct the heat transfer devices of the present technology; and thereduction of gastric pressure through gastric ventilation.

Following cooling, the set point temperature of the heat transfer mediumwas switched to a warming mode (42° C.).

To further simulate the hypothermia inducing conditions of the operatingroom, the swine was left exposed to the ambient temperature of the room(22° C.), continuously anesthetized with inhalational anesthesia,paralyzed with a non-depolarizing paralytic to prevent shivering, andprovided with a continuous flow of maintenance room temperatureintravenous fluid hydration.

Data from the warming and maintenance phase of the experiment are shownin Table 3. The data in Table 3 demonstrate an initial maintenance ofthe swine body temperature at 33.6° C., followed by a successful safe,gradual increase in body temperature for the duration of the experiment.FIG. 9 shows the total amount of heat transferred, as calculated above,during the warming and maintenance phase of the experiment.

TABLE 3 Operative Temperature Management and Warming Time (min) RectalTemperature (° C.) 0 33.6 5 33.6 10 33.6 15 33.7 20 33.7 25 33.8 30 33.835 33.8 40 33.8 45 33.8 50 33.9 55 33.9 60 33.9 65 33.9 70 33.9 85 34100 34.1 115 34.2 130 34.3 145 34.3 160 34.3 175 34.4 190 34.5 205 34.5

Consequently, the data demonstrate that a heat transfer device of thepresent technology can maintain, and increase, body temperature whilethe patient is exposed to adverse hypothermic conditions of an operatingroom environment.

Specific Embodiments

The devices, methods, and systems described herein can be illustrated bythe following embodiments enumerated in the numbered paragraphs thatfollow:

1. A method for inducing systemic hypothermia comprising:

inserting a heat transfer device into an esophagus of a patient, whereinsaid heat transfer device includes a fluid path defined by an inflowlumen and an outflow lumen;

initiating flow of a cooling medium along said fluid path; and

circulating said medium along said fluid path for a time sufficient toinduce systemic hypothermia in said patient.

2. The method of paragraph 1, wherein said heat transfer device includesa discrete heat transfer region and said heat transfer region isconfined to said esophagus.

3. The method of paragraph 1, further comprising cooling said medium toa temperature below normothermia.

4. The method of paragraph 1, further comprising maintaining saidpatient in a state of hypothermia for at least two hours.

5. The method of paragraph 1, further comprising monitoring at least onephysiological parameter of said patient.

6. The method of paragraph 5, wherein said at least one physiologicalparameter is body temperature.

7. The method of paragraph 6, further comprising maintaining said bodytemperature below about 34° C.

8. The method of paragraph 7, further comprising maintaining said bodytemperature between about 32° C. to about 34° C.

9. An esophageal heat transfer device comprising:

(a) a plurality of lumens configured to provide a fluid path for flow ofa heat transfer medium;

(b) a proximal end including an input port and an output port;

(c) a distal end configured for insertion into an esophagus of apatient.

10. The heat transfer device of paragraph 9, further comprising a hollowtube having a distal end configured to extend into a stomach of saidpatient.

11. The heat transfer device of paragraph 9, further comprising ananti-bacterial coating.

12. The heat transfer device of paragraph 9, further comprising anexpandable balloon.

13. A method for treating or preventing injury caused by an ischemiccondition comprising:

inserting a heat transfer device into an esophagus of a patient, whereinsaid heat transfer device includes a fluid path defined by an inflowlumen and an outflow lumen;

initiating flow of a cooling medium along said fluid path; and

circulating said medium along said fluid path for a time sufficient toinduce systemic hypothermia in said patient.

14. A method for treating or preventing ischemia-reperfusion injurycomprising:

inserting a heat transfer device into an esophagus of a patient, whereinsaid heat transfer device includes a fluid path defined by an inflowlumen and an outflow lumen;

initiating flow of a cooling medium along said fluid path; and

circulating said medium along said fluid path for a time sufficient toinduce systemic hypothermia in said patient.

15. A method for treating or preventing neurological injury comprising:

inserting a heat transfer device into an esophagus of a patient, whereinsaid heat transfer device includes a fluid path defined by an inflowlumen and an outflow lumen;

initiating flow of a cooling medium along said fluid path; and

circulating said medium along said fluid path for a time sufficient toinduce systemic hypothermia in said patient.

16. The method of paragraph 15, wherein said neurological injury isassociated with stroke, traumatic brain injury, spinal cord injury,subarachnoid hemorrhage, out-of-hospital cardiopulmonary arrest, hepaticencephalopathy, perinatal asphyxia, hypoxic-anoxic encephalopathy,infantile viral encephalopathy, near-drowning, anoxic brain injury,traumatic head injury, traumatic cardiac arrest, newbornhypoxic-ischemic encephalopathy, hepatic encephalopathy, bacterialmeningitis, cardiac failure, post-operative tachycardia, or acuterespiratory distress syndrome.

17. The method of paragraph 16, wherein said stroke is ischemic stroke.

18. A method for treating or preventing cardiac injury comprising:

inserting a heat transfer device into an esophagus of a patient, whereinsaid heat transfer device includes a fluid path defined by an inflowlumen and an outflow lumen;

initiating flow of a cooling medium along said fluid path; and

circulating said medium along said fluid path for a time sufficient toinduce systemic hypothermia in said patient.

19. A method for treating myocardial infarction comprising:

inducing mild therapeutic hypothermia.

20. A method for treating stroke comprising:

inducing mild therapeutic hypothermia.

21. A method for treating traumatic brain injury comprising:

inducing mild therapeutic hypothermia.

22. A method for treating Acute Respiratory Distress Syndromecomprising:

inducing mild therapeutic hypothermia.

23. The method of any one of paragraphs 19-22, wherein said hypothermiais systemic hypothermia.

24. The method of any one of paragraphs 19-22, wherein said hypothermiais induced via esophageal cooling.

25. The method of any one of paragraphs 19-22, further comprisingmaintaining said patient in a state of hypothermia for at least twohours.

26. The method of paragraph 25, further comprising maintaining saidpatient in a state of hypothermia for at least twenty-four hours.

27. The method of paragraph 26, further comprising maintaining saidpatient in a state of hypothermia for at least seventy-two hours.

28. The method of any one of paragraphs 19-22, further comprisingmonitoring at least one physiological parameter of said patient.

29. The method of paragraph 28, wherein said at least one physiologicalparameter is body temperature.

30. The method of paragraph 29, further comprising maintaining said bodytemperature below about 34° C.

31. The method of paragraph 30, further comprising maintaining said bodytemperature between about 32° C. to about 34° C.

32. The method of paragraph 24, further comprising:

inserting a heat transfer device into an esophagus of a patient, whereinsaid heat transfer device includes a fluid path defined by an inflowlumen and an outflow lumen;

initiating flow of a cooling medium along said fluid path; and

circulating said medium along said fluid path for a time sufficient toinduce systemic hypothermia in said patient.

33. A method for treating cardiac arrest comprising:

inducing systemic hypothermia via esophageal cooling.

34. The method of paragraph 33, further comprising:

inserting a heat transfer device into an esophagus of a patient, whereinsaid heat transfer device includes a fluid path defined by an inflowlumen and an outflow lumen;

initiating flow of a cooling medium along said fluid path; and

circulating said medium along said fluid path for a time sufficient toinduce systemic hypothermia in said patient.

35. A device for cooling or warming at least one portion of a patient'sbody, comprising:

a heat transfer device including a proximal end, a distal end, and atleast one flexible tube extending therebetween;

said proximal end including a heat transfer medium input port and a heattransfer medium output port;

said distal end configured for insertion into an orifice of a patient;

said at least one flexible tube defining an inflow lumen and an outflowlumen;

said lumens configured to provide a fluid path for flow of a heattransfer medium;

a supply line connected to said input port; and

a return line connected to said output port.

36. The device of paragraph 35, wherein said heat transfer medium is acooling medium.

37. A method of using the device of paragraph 36 to treat or preventinjury caused by an ischemic condition comprising:

inserting the distal end of the heat transfer device nasally or orally;

advancing said distal end into an esophagus;

initiating flow of a cooling medium along said fluid path; and

circulating said medium along said fluid path for a time sufficient toinduce systemic hypothermia in said patient.

38. A method of using the device of paragraph 36 to treat or preventischemia-reperfusion injury comprising:

inserting the distal end of the heat transfer device nasally or orally;

advancing said distal end into an esophagus;

initiating flow of a cooling medium along said fluid path; and

circulating said medium along said fluid path for a time sufficient toinduce systemic hypothermia in said patient.

39. A method of using the device of paragraph 36 to treat or preventneurological injury comprising:

inserting the distal end of the heat transfer device nasally or orally;

advancing said distal end into an esophagus;

initiating flow of a cooling medium along said fluid path; and

circulating said medium along said fluid path for a time sufficient toinduce systemic hypothermia in said patient.

40. A method of using the device of paragraph 36 to treat or preventcardiac injury comprising:

inserting the distal end of the heat transfer device nasally or orally;

advancing said distal end into an esophagus;

initiating flow of a cooling medium along said fluid path; and

circulating said medium along said fluid path for a time sufficient toinduce systemic hypothermia in said patient.

41. A method of using the device of paragraph 36 to treat myocardialinfarction comprising:

inserting the distal end of the heat transfer device nasally or orally;

advancing said distal end into an esophagus;

initiating flow of a cooling medium along said fluid path; and

circulating said medium along said fluid path for a time sufficient toinduce systemic hypothermia in said patient.

42. A method of using the device of paragraph 36 to treat strokecomprising:

inserting the distal end of the heat transfer device nasally or orally;

advancing said distal end into an esophagus;

initiating flow of a cooling medium along said fluid path; and

circulating said medium along said fluid path for a time sufficient toinduce systemic hypothermia in said patient.

43. A method of using the device of paragraph 36 to treat traumaticbrain injury comprising:

inserting the distal end of the heat transfer device nasally or orally;

advancing said distal end into an esophagus;

initiating flow of a cooling medium along said fluid path; and

circulating said medium along said fluid path for a time sufficient toinduce systemic hypothermia in said patient.

44. A method of using the device of paragraph 36 to treat AcuteRespiratory Distress Syndrome comprising:

inserting the distal end of the heat transfer device nasally or orally;advancing said distal end into an esophagus;

initiating flow of a cooling medium along said fluid path; and

circulating said medium along said fluid path for a time sufficient toinduce systemic hypothermia in said patient.

45. The method of any one of paragraphs 37-44, further comprisingcooling said medium to a temperature below normothermia.

46. The method of any one of paragraphs 37-44, further comprisingmaintaining said patient in a state of hypothermia for at least twohours.

47. The method of paragraph 46, further comprising maintaining saidpatient in a state of hypothermia for at least twenty-four hours.

48. The method of paragraph 47, further comprising maintaining saidpatient in a state of hypothermia for at least seventy-two hours.

49. The method of any one of paragraphs 37-44, further comprisingmonitoring at least one physiological parameter of said patient.

50. The method of paragraph 49, wherein said at least one physiologicalparameter is body temperature.

51. The method of paragraph 50, further comprising maintaining said bodytemperature below about 34° C.

52. The method of paragraph 51, further comprising maintaining said bodytemperature between about 32° C. to about 34° C.

53. A method for controlling core body temperature in a patientcomprising:

inserting a heat transfer device into an esophagus of a patient, whereinsaid heat transfer device includes a fluid path defined by an inflowlumen and an outflow lumen;

initiating flow of a heat transfer medium along said fluid path; and

circulating said medium along said fluid path for a time sufficient tocontrol core body temperature in said patient.

54. The method of paragraph 53, wherein said heat transfer deviceincludes a discrete heat transfer region and said heat transfer regionis confined to said esophagus.

55. The method of paragraph 53, further comprising cooling said mediumto a temperature below normothermia.

56. The method of paragraph 53, further comprising warming said mediumto a temperature above normothermia.

57. The method of paragraph 53, further comprising maintaining saidpatient in a state of hypothermia for at least two hours.

58. The method of paragraph 53, further comprising maintaining saidpatient at normothermia for at least two hours.

59. The method of paragraph 53, further comprising monitoring at leastone physiological parameter of said patient.

60. The method of paragraph 59, wherein said at least one physiologicalparameter is body temperature.

61. The method of paragraph 53, further comprising maintaining said bodytemperature below about 34° C.

62. The method of paragraph 53, further comprising maintaining said bodytemperature between about 32° C. to about 34° C.

63. The method of paragraph 53, further comprising maintaining said bodytemperature at about 37° C.

64. A method for operative temperature management comprising:

inserting a heat transfer device into an esophagus of a patient, whereinsaid heat transfer device includes a fluid path defined by an inflowlumen and an outflow lumen;

initiating flow of a heat transfer medium along said fluid path; and

circulating said medium along said fluid path for a time sufficient tomanage core body temperature in said patient.

65. The method of paragraph 64, further comprising maintaining saidpatient in a state of hypothermia for at least two hours.

66. The method of paragraph 64, further comprising maintaining said bodytemperature below about 34° C.

67. The method of paragraph 64, further comprising maintaining said bodytemperature between about 32° C. to about 34° C.

68. The method of paragraph 64, further comprising maintaining saidpatient in a state of normothermia for at least two hours.

69. The method of paragraph 64, further comprising maintaining said bodytemperature at about 37° C.

70. The method of paragraph 64, further comprising monitoring at leastone physiological parameter of said patient.

71. The method of paragraph 70, wherein said at least one physiologicalparameter is body temperature.

The presently described technology is now described in such full, clear,concise and exact terms as to enable any person skilled in the art towhich it pertains, to practice the same. It is to be understood that theforegoing describes preferred embodiments of the technology and thatmodifications may be made therein without departing from the spirit orscope of the invention as set forth in the appended claims.

1. A method for controlling core body temperature in a patient comprising: inserting a heat transfer device into an esophagus of a patient, wherein the heat transfer device includes a fluid path defined by an inflow lumen and an outflow lumen; initiating flow of a heat transfer medium along the fluid path; and circulating the medium along the fluid path for a time sufficient to control core body temperature in the patient.
 2. The method of claim 1, wherein the heat transfer device includes a discrete heat transfer region and the heat transfer region is confined to the esophagus.
 3. The method of claim 1, further comprising cooling the medium to a temperature below normothermia.
 4. The method of claim 1, further comprising warming the medium to a temperature above normothermia.
 5. The method of claim 1, further comprising maintaining the patient in a state of hypothermia for at least about two hours.
 6. The method of claim 1, further comprising maintaining the patient at normothermia for at least about two hours.
 7. The method of claim 1, further comprising monitoring at least one physiological parameter of the patient.
 8. The method of claim 1, further comprising maintaining the patient's body temperature below about 34° C.
 9. The method of claim 1, further comprising maintaining the patient's body temperature between about 32° C. to about 34° C.
 10. The method of claim 1, further comprising maintaining the patient's body temperature at about 37° C.
 11. A method for operative temperature management comprising: inserting a heat transfer device into an esophagus of a patient, wherein the heat transfer device includes a fluid path defined by an inflow lumen and an outflow lumen; initiating flow of a heat transfer medium along the fluid path; and circulating the medium along the fluid path for a time sufficient to manage core body temperature in the patient.
 12. The method of claim 11, further comprising maintaining the patient in a state of hypothermia for at least about two hours.
 13. The method of claim 11, further comprising maintaining the patient's body temperature below about 34° C.
 14. The method of claim 11, further comprising maintaining the patient's body temperature between about 32° C. to about 34° C.
 15. The method of claim 11, further comprising maintaining the patient in a state of normothermia for at least about two hours.
 16. The method of claim 11, further comprising maintaining the patient's body temperature at about 37° C.
 17. The method of claim 11, further comprising monitoring at least one physiological parameter of the patient.
 18. A method for treating or preventing ischemia-reperfusion injury; neurological injury; or cardiac injury comprising: inserting a heat transfer device into an esophagus of a patient, wherein the heat transfer device includes a fluid path defined by an inflow lumen and an outflow lumen; initiating flow of a cooling medium along the fluid path; and circulating the medium along the fluid path for a time sufficient to induce systemic hypothermia in the patient.
 19. The method of claim 18, wherein the hypothermia is systemic hypothermia.
 20. The method of claim 18, wherein the hypothermia is induced via esophageal cooling.
 21. The method of claim 18, further comprising maintaining the patient in a state of hypothermia for at least about two hours.
 22. The method of claim 18, further comprising maintaining the patient in a state of hypothermia for at least about twenty-four hours.
 23. The method of claim 18, further comprising maintaining the patient in a state of hypothermia for at least about seventy-two hours.
 24. The method of claim 18, further comprising monitoring at least one physiological parameter of the patient.
 25. The method of claim 18, further comprising maintaining the patient's body temperature below about 34° C.
 26. The method of claim 18, further comprising maintaining the patient's body temperature between about 32° C. to about 34° C. 